Two-Step Enzymatic Synthesis of beta-D-N-Acetylgalactosamine-(1 -> 4)-D-N-acetylglucosamine (LacdiNAc) Chitooligomers for Deciphering Galectin Binding Behavior

0476013 - MBÚ 2018 RIV DE eng J - Článek v odborném periodiku
Laaf, D. - Bojarová, Pavla - Mikulová, Barbora - Pelantová, Helena - Křen, Vladimír - Elling, L.
Two-Step Enzymatic Synthesis of beta-D-N-Acetylgalactosamine-(1 -> 4)-D-N-acetylglucosamine (LacdiNAc) Chitooligomers for Deciphering Galectin Binding Behavior.
Advanced Synthesis & Catalysis. Roč. 359, č. 12 (2017), s. 2101-2108. ISSN 1615-4150. E-ISSN 1615-4169
Grant CEP: GA ČR GC15-02578J
Institucionální podpora: RVO:61388971
Klíčová slova: chitooligomers * galectin-3 * glycoside hydrolase
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 5.123, rok: 2017

A two-step synthesis of engineered variants of Talaromyces flavus Beta-N-acetylhexosaminidase (TfHexY470N) and human beta4-galactosyltransferase (beta4GalTY284L) yielded complex glycans comprising a chitooligomeric spacer (beta1,4GlcNAc)n=0-3 terminated with a beta4-linked beta-d-N-acetylgalactosamine-(1-4)-d-N-acetylglucosamine (LacdiNAc) epitope. These compounds are novel inhibitors of human galectin-3 (Gal-3), a widely spread animal lectin with important physiological functions in cellular communication. The multivalent presentation of glycan oligomers was accomplished by chemical conjugation of glycans to lysine residues of bovine serum albumin (BSA). Binding studies of Gal-3 to immobilized BSA neo-glycoconjugates revealed the beneficial influence of the chitooligomeric spacer for the ligand-lectin affinity. We conclude that the use of the (beta1,4GlcNAc)n=0–3 spacer is a perfect nature-like solution for the presentation of elaborated Gal-3 glycan epitopes that surpasses the performance of commonly used synthetic spacers.
Trvalý link: http://hdl.handle.net/11104/0272585